Studies Seek to Expand on PARP Inhibitor Success in Ovarian Cancer

With 3 PARP inhibitors available for patients with recurrent ovarian cancer and in the maintenance setting, Susana Campos, MD, MPH, said that ongoing clinical trials will answer questions about where the future management of the disease is headed.

Such queries could be addressed in 2019, following the practice-changing data of the phase III SOLO-1 trial that were presented at the 2018 ESMO Congress. In the study, the PARP inhibitor olaparib (Lynparza) reduced the risk of disease progression or death by 70% in patients with BRCA-mutant advanced ovarian cancer who were in complete or partial response to platinum-based chemotherapy (HR, 0.30; 95% CI, 0.23-0.41; P <.0001) versus placebo following chemotherapy.

The FDA approved olaparib in December 2018 as a maintenance therapy for patients with deleterious or suspected deleterious germline or somatic BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to frontline platinum-based chemotherapy.

“The SOLO-1 trial really opened our eyes that there is a tomorrow for patients with ovarian cancer,” said Campos, an assistant professor of medicine, Harvard Medical School, and Dana-Farber Cancer Institute.

Following the single-agent PARP inhibition activity, clinical trials are ongoing to determine the efficacy with them in combination with antiangiogenic agents, immunotherapy, and chemotherapy, Campos explained. One such trial, ATHENA (NCT03522246), is evaluating the combination of rucaparib (Rubraca) and nivolumab (Opdivo) as maintenance therapy following first-line platinum-based chemotherapy.

In an interview during the 2018 OncLive® State of the Science SummitTM on Ovarian Cancer, Campos highlighted the success with PARP inhibitors in the relapsed and maintenance ovarian cancer settings.

OncLive: Could you highlight the key takeaways from your presentation on PARP inhibitors?

Campos: We talked about PARP inhibitors and how they have infiltrated the world of ovarian cancer, and in many ways how they have changed the course of ovarian cancer. I spoke a bit about what some of the PARP inhibitors are in the recurrent setting as single agents—where it all started.

Then, I moved onto maintenance therapy, which is an extremely important area. We do a great job of treating women with ovarian cancer and putting them into remission, but the disease in of itself doesn’t stay in remission. Some of the studies, NOVA, SOLO-2, Study 19, and ARIEL3 showed us that we can keep individuals in remission a little longer.

We also spoke about interesting data about the SOLO-1 trial, which was a highlight of the 2018 ESMO Congress. Then, we talked about if PARP inhibitors work as single agents, what if we were to combine them with other agents, such as antiangiogenic agents? In terms of immunotherapy, my colleague [Panagiotis A. Konstantinopoulos, MD] also spoke on PARP inhibitors and immunotherapy. Therefore, in my lecture, we talked about where [PARP inhibition] started, where it is today, and where we think we're going tomorrow [with them].

The SOLO-1 trial had practice-changing findings. Could you highlight that study and the data?

The SOLO-1 trial was specifically in BRCA-mutation carriers, so patients in the upfront setting, after they finished chemotherapy and if they were in complete remission, were subsequently randomized to an intervention, which in this case was olaparib or placebo, and they were followed.

They were on treatment for about 2 years, and in a landmark analysis of about 3 years, it was striking because of the patients who were randomized to olaparib, at least 60% were progression free at that time as opposed to about 24% [who had placebo]. This is statistically significant. Where this pans out in the future, [the question is], does it improve OS? It is too early to tell. These are not mature results, but at least at first blush, these are incredibly exciting data. Everyone in the room understands and gets a chill when they actually see these data.

What are the differences between the 3 available PARP inhibitors?

We know, in essence, that they are pretty similar. There are olaparib, niraparib (Zejula), and rucaparib. There are going to be more at the end of the day. We know that they have some common side effects; for example, there is anemia, thrombocytopenia, and leukopenia. We know that there are gastrointestinal toxicities, but some of them have some unique toxicities.